Pain, an unpleasant sensory and emotional experience, is a significant often under-recognized medical problem spanning numerous patient populations. One of the leading causes for individuals to seek medical attention is musculoskeletal pain. Indeed, pain is now considered the 5th vital sign. Unfortunately, pain is highly variable between individuals. In both acute and chronic pain conditions, there is often a dissociation of pain perception and the underlying pathology in a variety of conditions such as low back pain, osteoporosis or osteoarthritis. Significant pain that is disproportionate to the physical findings is challenging to treat and can result in decreased quality of life and greater disability. Thus, pain heterogeneity associated with common clinical conditions Interferes with diagnosis and adequate treatment, ultimately compromising healthcare. The biopsychosocial model of pain suggests pain perception is a complex process that involves a myriad of physical, social, and emotional components. While no one factor can explain pain heterogeneity, individual differences in gender, genotype, and psychological traits may play a significant role. Unfortunately, it is difficult to find individuals with adequate multidisciplinary training to investigate pain from a multi-factorial perspective. Thus, the goal of the proposed research and training is to gain the expertise to determine the degree to which measurable Individual differences, e.g. sex, genotype and personality traits, predict high and low pain responses. This translational study approach utilizes a controlled, deep-tissue, algesic stimulus in human subjects to critically examine factors that contribute to pain heterogeneity. The Intramuscular infusion of an acidic phosphate buffer provides a clinically-relevant nociceptive stimulus of deep-tissue pain. This novel model provides a unique opportunity to study the Influence of baseline individual differences without the confounding factors associated with clinical pain syndromes. RELEVANCE: Musculoskeletal pain is a prevalent problem in our society and pain heterogeneity between individuals may result from multiple factors. This research plan will assess the role of normal personality traits, sex, and genotype on muscle pain sensitivity. This information may improve diagnosis and treatment strategies for musculoskeletal pain, advancing healthcare through increasingly individualized patient care approaches.